A low molecular weight, noncytotoxic, species-independent, chalone- like inhibitor of lymphocyte proliferation is released from metabolizing rat spleen cells in vitro. Large volumes of splenic supernatant will be produced and the inhibitor purified by molecular sieve and ion exchange chromatography. Its effects on human lymphoid tumor lines and lymphocytes from patients with acute leukemia and lymphoma will be compared with its effects on normal lymphocytes, by determining the dilution of inhibitor required to comparably decrease the uptake of H3-thymidine and the mitotic index of each target cell. Its in vivo effects on the recurrent growth of a murine lymphoid ascites tumor will be studied. The production of this inhibitor by malignant versus normal lymphocytes will be compared. Lymphoma and plasmacytoma cell lines, and porcine and bovine spleen cells will be screened to determine if these can be used to produce large quantities for purification and use in the chemotherapy of patients with lymphoid malignancies.